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Saturday, November 1, 2008

Common Genetic Origins for EEG, Alcoholism and Anxiety: The Role of CRH-BP
PLoS ONE 3(10): e3620.

The resting EEG is a dynamic index of cortical activation, cognitive function and consciousness and is therefore an intermediate phenotype for many behaviors in which arousal is implicated such as anxiety and alcoholism.

We performed a dense whole genome linkage scan using 3878 unlinked SNPs in a large pedigree derived from a population isolate sample of 328 Plains American Indians.

Alpha (8–13 Hz), theta (4–8 Hz) and beta (13–30 Hz) EEG power was heritable (0.58–0.27) and stable over a 2 year period (r = 0.82–0.53). Genetic correlations between frequency bands were high (0.75). Linkage peaks for EEG power in all three frequency bands converged on chromosome 5q13-14 with genome-wide significant LOD scores of 3.5 (empirical p<0.0001) for alpha and beta power.

A logical candidate gene, corticotropin releasing hormone-binding protein (CRH-BP), was located at the apex of these convergent linkage peaks. CRH-BP was significantly associated with alpha power in the Plains Indians and also in a replication sample of 188 Caucasians. Moreover, the same SNPs and haplotypes, located within the CRH-BP haplotype block, were also associated with anxiety disorders in the Plains Indians and alcohol use disorders in the Caucasians.

modulates CRH which influences cortical and hippocampal EEG activity and is the primary mediator of the neuroendocrine stress response.

Our results suggest a likely role for CRH-BP in stress-related alcoholism and highlight the use of the resting EEG as an intermediate phenotype for arousal-related behaviors such as anxiety and addiction.

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